Brief Title
Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B
Official Title
A Phase I, Open-Label, Ascending Dose Study to Assess the Safety and Tolerability of AAV2/6 Factor IX Gene Therapy Via Zinc Finger Nuclease (ZFN) Mediated Targeted Integration of SB-FIX in Adult Subjects With Severe Hemophilia B
Brief Summary
The purpose of the study is to evaluate the safety, tolerability and effect on FIX antigen and activity levels of ascending doses of SB-FIX. SB-FIX is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the Factor 9 gene into the albumin locus in hepatocytes with the goal of lifelong therapeutic production of the Factor IX clotting factor.
Detailed Description
The objective of the study is to provide long term expression of Factor IX in subjects with severe hemophilia B. SB-FIX is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-FIX is intended to function by placement of a corrective copy of the Factor IX transgene into the genome of the subject's own hepatocytes, under the control of the highly expressed endogenous albumin locus, and is expected to provide permanent, liver-specific expression of Factor IX for the lifetime of a hemophilia B subject.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Treatment related Adverse Events in subjects who received SB-FIX as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Secondary Outcome
Change from baseline in FIX antigen and activity levels
Condition
Hemophilia B
Intervention
SB-FIX
Study Arms / Comparison Groups
Cohort 1
Description: SB-FIX: Low Dose
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
1
Start Date
November 15, 2016
Completion Date
April 19, 2021
Primary Completion Date
April 19, 2021
Eligibility Criteria
Inclusion Criteria: - Male >18 years of age - Severe hemophilia B (native circulating FIX activity <1%, with or without cross reactive material) Exclusion Criteria: - Presence of neutralizing antibodies - History of hypersensitivity response or an allergic reaction to FIX or FIX products - Currently receiving long acting FIX replacement therapy - FIX mutations known to be associated with FIX inhibitors - Polymorphisms in the ZFN target region - Presence of any liver mass on MRI, or elevated alpha-fetoprotein (AFP) - Any contraindication to the use of corticosteroids for immunosuppression - Currently receiving antiviral therapy for hepatitis B or C or with history or active hepatitis B or hepatitis C or HIV-1 or HIV1/2 antibody positive. - Chronic anemia, leukopenia, or thrombocytopenia - Past medical history of active tuberculosis or significant fungal disease - Symptomatic cardiovascular disease as a co-morbid condition - Markers of hepatic inflammation or overt or occult cirrhosis - History of chronic renal disease or creatinine ≥ 1.5 mg/dL - Systemic (iv or oral) immunomodulatory agent or steroid use (topical treatment is allowed) - History of chronic infection or other chronic disorder considered an unacceptable risk - History of malignancy except for treated basal cell or squamous cell carcinoma - History of alcohol or substance abuse - Previously received gene therapy product - Participation in prior investigational drug or medical device study within the previous 3 months - History of therapeutic non-adherence - Any other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for participation in the study
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Medical Monitor, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02695160
Organization ID
SB-FIX-1501
Responsible Party
Sponsor
Study Sponsor
Sangamo Therapeutics
Study Sponsor
Medical Monitor, Study Director, Sangamo Therapeutics, Inc.
Verification Date
March 2022